A Precision Medicine Approach Using Gene Silencing to Treat a Chronic Liver Disease Called Non-Alcoholic Steatohepatitis (NASH) in Adult Participants at Increased Genetic Risk for This Condition (NASHGEN-2)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Non-alcoholic Steatohepatitis (NASH); Metabolic Dysfunction Associated Steatohepatitis (MASH)

Treatments: Drug: Placebo; Drug: ALN-HSD

Study type: Interventional

Funder types: Industry

Identifiers

NCT05519475

ALN-HSD-NASH-2130

Details and patient eligibility

About

This study is researching an investigational drug called ALN-HSD (called "study drug"). This study is focused on participants who are known to have non-alcoholic steatohepatitis (NASH). NASH is a form of non-alcoholic fatty liver disease (NAFLD). Recently, the name metabolic dysfunction associated steatohepatitis (MASH) has been introduced to replace NASH and metabolic dysfunction-associated steatotic liver disease (MASLD) to replace NAFLD. NASH occurs when fat builds up in liver cells, damaging them, and making the liver inflamed and stiff from fibrosis (scar tissue). NASH can progress to cirrhosis (long term scarring) and liver failure (when the liver cannot perform its job). The aim of the study is to see the effect of the study drug on lessening liver scarring side effects related to NASH.

The study is looking at several other research questions, including:

• How the study drug works to improve liver function and lessen NASH related inflammation in the liver
• What side effects may happen from receiving the study drug
• How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in the blood at different times
• Better understanding of the study drug and NASH

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Adult male or female ≥18 years (or country's legal age of adulthood)
2. A diagnosis of NASH with fibrosis (F) stage 2 or 3
3. NAS score ≥4 according to the NASH CRN histological scoring system
4. Meets genotype criteria for study enrollment, as defined in the protocol

Key Exclusion Criteria:

1. Evidence of other forms of known chronic liver disease, as defined in the protocol
2. Known history of alcohol or other substance abuse within the last year or at any time during screening
3. History of Type 1 diabetes
4. Bariatric surgery within approximately 5 years prior to or planned during the study period
5. Prior exposure to any investigational drug targeting HSD17B13 or patatin-like phospholipase domain containing 3 (PNPLA3) (eg, ALN-HSD or ARO-HSD, AZD2693)

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

ALN-HSD

Experimental group

Description:

Randomized 1:1

Treatment:

Drug: ALN-HSD

Placebo

Placebo Comparator group

Description:

Randomized 1:1

Treatment:

Drug: Placebo